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Identification
NameDaclizumab
Accession NumberDB00111  (BIOD00007, BTD00007)
TypeBiotech
GroupsApproved, Investigational
Description

Humanized IgG1 Mab that binds to the human interleukin-2 receptor (anti-Tac or anti-CD25). Daclizumab is a composite of human (90%) and murine (10%) antibody sequences. The human sequences were derived from the constant domains of human IgG1 and the variable framework regions of the Eu myeloma antibody. The murine sequences were derived from the complementarity-determining regions of a murine anti-Tac antibody.

Protein structureDb00111
Protein chemical formulaC6332H9808N1678O1989S42
Protein average weight142612.1000
Sequences
>Humanized Anti-CD25 Heavy Chain 1
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYRMHWVRQAPGQGLEWIGYINPSTGYTEY
NQKFKDKATITADESTNTAYMELSSLRSEDTAVYYCARGGGVFDYWGQGTTLTVSSGPSV
FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
VTVPSSSLGTQTYICNVNHKPSNTKVDKKAEPKSCDKTHTCPPCPAPELLGGPSVFLFPP
KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV
LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL
TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGK
>Humanized Anti-CD25 Light Chain 1
DIQMTQSPSTLSASVGDRVTITCSASSSISYMHWYQQKPGKAPKLLIYTTSNLASGVPAR
FSGSGSGTEFTLTISSLQPDDFATYYCHQRSTYPLTFGSGTKVEVKRTVAAPSVFIFPPS
DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
SKADYEKHKVYACEVTHQGLSSPVTKSFNR
Download FASTA Format
Synonyms
SynonymLanguageCode
Anti-IL-2Not AvailableNot Available
Humanized antiCD25Not AvailableNot Available
Ig gamma-1 chain C regionNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
ZenapaxHoffmann-La Roche Inc
Brand mixturesNot Available
Categories
CAS number152923-56-3
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationZenapax is a humanized monoclonal antibody used for prevention of renal transplant rejection
PharmacodynamicsZenapax functions as an IL-2 receptor antagonist. Specifically it inhibits IL-2-mediated activation of lymphocytes, a critical pathway in the cellular immune response involved in allograft rejection.
Mechanism of actionZenepax binds with high-affinity to the Tac subunit of the high-affinity IL-2 receptor complex and inhibits IL-2 binding. The IL-2 receptor (Tac) subunit is expressed on activated but not resting lymphocytes.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Most likely removed by opsonization via the reticuloendothelial system when bound to lymphocytes.

Route of eliminationNot Available
Half life11-38 days
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
LiquidIntravenous
PricesNot Available
PatentsNot Available
Properties
Stateliquid
Experimental Properties
PropertyValueSource
melting point61 °C (FAB fragment), 71 °C (whole mAb)Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
hydrophobicity-0.437Not Available
isoelectric point8.46Not Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
UniProtP01857
GenbankJ00228
PharmGKBPA164764446
Drug Product Database2241473
RxListhttp://www.rxlist.com/cgi/generic3/zenapax.htm
Drugs.comhttp://www.drugs.com/cdi/daclizumab.html
WikipediaDaclizumab
ATC CodesL04AC01
AHFS Codes
  • 92:00.00
PDB Entries
FDA labelshow(666 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
Rilonaceptresults in increased immunosuppressive effects; increases the risk of infection.
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food InteractionsNot Available

Targets

1. Interleukin-2 receptor subunit alpha

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antibody

Components

Name UniProt ID Details
Interleukin-2 receptor subunit alpha P01589 Details

References:

  1. Shamsi TS, Irfan M, Farzana T, Ansari SH, Ahmad G, Shakoor N, Baig MI: Allogeneic peripheral blood stem cell transplant (PBSCT) using anti-IL2 receptor antibody Daclizumab for the prevention of acute graft versus host disease in steroid refractory Diamond Blackfan anaemia: a case report. J Pak Med Assoc. 2005 Oct;55(10):454-5. Pubmed
  2. Przepiorka D, Kernan NA, Ippoliti C, Papadopoulos EB, Giralt S, Khouri I, Lu JG, Gajewski J, Durett A, Cleary K, Champlin R, Andersson BS, Light S: Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. Blood. 2000 Jan 1;95(1):83-9. Pubmed
  3. Garcia CD, Bittencourt VB, Tumelero A, Antonello JS, Malheiros D, Garcia VD: Plasmapheresis for recurrent posttransplant focal segmental glomerulosclerosis. Transplant Proc. 2006 Jul-Aug;38(6):1904-5. Pubmed
  4. Krouwels FH, van der Heijden JF, Lutter R, van Neerven RJ, Jansen HM, Out TA: Glucocorticosteroids affect functions of airway- and blood-derived human T-cell clones, favoring the Th1 profile through two mechanisms. Am J Respir Cell Mol Biol. 1996 Apr;14(4):388-97. Pubmed
  5. Patlolla V, Zhong X, Reed GW, Mandelbrot DA: Efficacy of anti-IL-2 receptor antibodies compared to no induction and to antilymphocyte antibodies in renal transplantation. Am J Transplant. 2007 Jul;7(7):1832-42. Pubmed
  6. Monti P, Brigatti C, Heninger AK, Scirpoli M, Bonifacio E: Disengaging the IL-2 receptor with daclizumab enhances IL-7-mediated proliferation of CD4 and CD8 T cells. Am J Transplant. 2009 Dec;9(12):2727-35. Epub 2009 Sep 25. Pubmed
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Interleukin-2 receptor subunit beta

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antibody

Components

Name UniProt ID Details
Interleukin-2 receptor subunit beta P14784 Details

References:

  1. Light JA, Sasaki TM, Ghasemian R, Barhyte DY, Fowlkes DL: Daclizumab induction/tacrolimus sparing: a randomized prospective trial in renal transplantation. Clin Transplant. 2002;16 Suppl 7:30-3. Pubmed
  2. Aguillon JC, Contreras J, Dotte A, Cruzat A, Catalan D, Salazar L, Molina MC, Guerrero J, Lopez M, Soto L, Salazar-Onfray F, Cuchacovich M: [New immunological weapons for medicine in the 21st Century: biological therapy based on the use of the latest generation monoclonal antibodies] Rev Med Chil. 2003 Dec;131(12):1445-53. Pubmed
  3. Forrest K, Logan B, Strange J, Roszman TL, Goebel J: Daclizumab therapy in kidney transplantation-different mechanisms of action in- versus ex-vivo? Transpl Immunol. 2005 Mar;14(1):43-7. Epub 2005 Jan 4. Pubmed
  4. Ramos EL, Milford EL, Kirkman RL, Tilney NL, Strom TB, Shapiro ME, Waldmann TA, Wood IG, Rollins MR, Carpenter CB: Differential IL-2 receptor expression in renal allograft recipients treated with an anti-IL-2-receptor antibody. Transplantation. 1989 Sep;48(3):415-20. Pubmed
  5. Burkhardt K, Mandel TE, Diamantstein T, Loughnan MS: Anti-IL-2 receptor monoclonal antibody AMT-13 increases soluble IL-2 receptor levels in vivo. Immunology. 1989 Feb;66(2):183-9. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Low affinity immunoglobulin gamma Fc region receptor III-B

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor III-B O75015 Details

References:

  1. Hoshino S, Oshimi K, Teramura M, Mizoguchi H: Activation via the CD3 and CD16 pathway mediates interleukin-2-dependent autocrine proliferation of granular lymphocytes in patients with granular lymphocyte proliferative disorders. Blood. 1991 Dec 15;78(12):3232-40. Pubmed
  2. Martelletti P, Stirparo G, De Stefano L, Di Sabato F, Giacovazzo M, Rinaldi-Garaci C: Defective expression of IL-2 receptors on peripheral blood lymphocytes from patients with cluster headache. Headache. 1990 Mar;30(4):228-31. Pubmed
  3. Galandrini R, Albi N, Tripodi G, Zarcone D, Terenzi A, Moretta A, Grossi CE, Velardi A: Antibodies to CD44 trigger effector functions of human T cell clones. J Immunol. 1993 May 15;150(10):4225-35. Pubmed
  4. Lanier LL, Kipps TJ, Phillips JH: Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen). J Exp Med. 1985 Dec 1;162(6):2089-106. Pubmed
  5. Hayakawa K, Salmeron MA, Kornbluth J, Bucana C, Itoh K: The role of IL-4 in proliferation and differentiation of human natural killer cells. Study of an IL-4-dependent versus an IL-2-dependent natural killer cell clone. J Immunol. 1991 Apr 1;146(7):2453-60. Pubmed

4. Complement C1r subcomponent

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1r subcomponent P00736 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

5. Complement C1q subcomponent subunit A

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1q subcomponent subunit A P02745 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

6. Complement C1q subcomponent subunit B

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1q subcomponent subunit B P02746 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

7. Complement C1q subcomponent subunit C

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1q subcomponent subunit C P02747 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

8. Low affinity immunoglobulin gamma Fc region receptor III-A

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor III-A P08637 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

9. High affinity immunoglobulin gamma Fc receptor I

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
High affinity immunoglobulin gamma Fc receptor I P12314 Details

References:

  1. Simms HH, Gaither TA, Fries LF, Frank MM: Monokines released during short-term Fc gamma receptor phagocytosis up-regulate polymorphonuclear leukocytes and monocyte-phagocytic function. J Immunol. 1991 Jul 1;147(1):265-72. Pubmed

10. Low affinity immunoglobulin gamma Fc region receptor II-a

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor II-a P12318 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

11. Low affinity immunoglobulin gamma Fc region receptor II-b

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor II-b P31994 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

12. Low affinity immunoglobulin gamma Fc region receptor II-c

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor II-c P31995 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on June 14, 2012 13:56